1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → methyl 5-[1-[4-[N'-(2-bromophenyl)ureido]-3-methoxyphenyl acetyl]-2-pyrrolidinylmethoxy]pyridine-2-carboxylate

HRID 354344Notes

Reaction equation

HRID 354344 reaction equation
[NH:1]1[CH2:5][CH2:4][CH2:3][CH:2]1[CH2:6][O:7][C:8]1[CH:9]=[CH:10][C:11]([C:14]([O:16][CH3:17])=[O:15])=[N:12][CH:13]=1.[Br:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=1[NH:25][C:26](=[O:40])[NH:27][C:28]1[CH:33]=[CH:32][C:31]([CH2:34][C:35](O)=[O:36])=[CH:30][C:29]=1[O:38][CH3:39].CCN=C=NCCCN(C)C.Cl>CN(C1C=CN=CC=1)C.CN(C=O)C>[Br:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=1[NH:25][C:26](=[O:40])[NH:27][C:28]1[CH:33]=[CH:32][C:31]([CH2:34][C:35]([N:1]2[CH2:5][CH2:4][CH2:3][CH:2]2[CH2:6][O:7][C:8]2[CH:9]=[CH:10][C:11]([C:14]([O:16][CH3:17])=[O:15])=[N:12][CH:13]=2)=[O:36])=[CH:30][C:29]=1[O:38][CH3:39]

Participants

6

Reactant 3

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 23511835Methyl 5-(2-pyrrolidinyl)methoxypyridine-2-carboxylateHCID 23512062HCID 23512062, compound

Product 1

HCID 69332272methyl 5-[1-[4-[N'-(2-bromophenyl)ureido]-3-methoxyphenyl acetyl]-2-pyrrolidinylmethoxy]pyridine-2-carboxylateYield 69.3%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Procedure

To a stirred mixture of methyl 5-(2-pyrrolidinyl)methoxypyridine-2-carboxylate (370 mg, 1.57 mmol), 4-[N′-(2-bromophenyl)ureido]-3-methoxyphenylacetic acid (595 mg, 1.57 mmol), 4-DMAP (230 mg, 1.88 mmol) in DMF (10 ml) was added EDC.HCl (360 mg, 1.88 mmol) at room temperature. The resulting mixture was stirred at room temperature for 20 hr. The mixture was pored into ice-water. The solid was collected, washed with water and air-dried. The crude solid was purified by silica-gel (30 ml) column chromatography with CHCl3—EtOH (98:2, v/v) as eluent and crystallized with Et2O to give methyl 5-[1-[4-[N′-(2-bromophenyl)ureido]-3-methoxypheny lacetyl]-2-pyrrolidinylmethoxy]pyridine-2-carboxylate (650 mg, 69%) as an amorphous solid. IR (KBr) n 3323, 1720, 1624, 1601, 1527 cm−1; 1H-NMR (CDCl3) δ1.22 and 2.00 (each m, 4 H), 3.48-4.55 (series of s and m, 13 H which contains amide-isomers), 6.93-8.82 (series of s and m, 12H which contains amide-isomers); MS (FAB) m/z 597 (M+−1) and 599 (M++1); Anal. Calcd. for C28H30BrN4O6.1.0×H2O: C, 54.55; H, 5.23; N, 9.09. Found: C, 54.13; H, 5.03; N, 9.33.

Workup

  1. customThe solid was collected
  2. washwashed with water
  3. customair-dried
  4. customThe crude solid was purified by silica-gel (30 ml) column chromatography with CHCl3—EtOH (98:2
  5. customv/v) as eluent and crystallized with Et2O

Sources & evidence

ORD record
ord-3d09795dee3643ceb54692a6b01c7733
Source dataset
uspto-grants-2004_06
Patent number
US06756378B2

Reaction notes

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